Oxygen permeable hard and semi-hard contact lens compositions, methods and articles of manufacture II

ABSTRACT

The invention relates to novel monomers of polysiloxanyl alkyl esters of acrylic and methacrylic acids and its copolymerization with alkyl esters of acrylic, methacrylic acids and/or itaconate esters to produce highly permeable contact lens material. The copolymer preferably includes a cross-linking agent and hydrophilic monomer. Contact lenses manufactured from the material are easily machined and polished into hard or semi-hard contact lenses having excellent dimensional stability.

BACKGROUND OF THE INVENTION

The present invention relates to novel chemical compounds, polymers madefrom such compounds and novel materials and products made from suchcompounds. Important use of the materials made from the invention is themanufacture of corneal contact lenses.

In recent years, corneal contact lenses have become more and morepopular in the United States and throughout the world.

The great popularity of contact lenses is easily understood. Oneimportant reason is that such lenses provide perhaps the best possiblemanner of achieving optical correction for the eyes. The lenses fitdirectly over the eye, and when properly fitted, are easily retained inplace. Problems common with spectacles, such as interference withperipheral vision, moving about on the head, discomfort, and thepossibility of improper interpupilary distance, are easily overcome.Contact lenses provide cosmetic advantages and afford convenience andincreased safety when used in diverse pursuits, particularly sportingevents.

Now most commonly used contact lenses are generally sudivided into twotypes, so-called hard contact lenses, and soft contact lenses. Each typeof lens has its own advantages, but each also includes certaindisadvantages.

Referring first to the advantages of hard contact lenses, these lensesprovide dimensional stability, so that the characteristics of an opticalprescription will remain unchanged while the lens is in use in the eye.In some cases, the eye will actually conform to the contour of the lensover a period of time so as to improve the vision of the wearer.Moreover, hard contact lenses are relatively durable in relation to softlenses.

While hard contact lenses have the above and other advantages, somepatients find such lenses somewhat uncomfortable in use, and prefer theso-called soft contact lens. These lenses fall generally into threecategories, namely lenses made from silicone rubber or like materials,lenses made from "HEMA" (hydroxyethylmethacrylate) or so-called"hydrogel" lenses, and finally, lenses of the methylmethacrylate basetype, modified by the addition of polymers such as cellulose acetatebutyrate ("CAB"). Soft lenses readily conform to the eye and are quitecomfortable in short term use. They are extremely thin as well as softand pliable. However, they do not provide satisfactory oxygentransmissibility through the lens.

Referring now to the disadvantage of both soft and hard contact lenses,neither type of lens is able to be worn by a user over an extendedperiod of time because both types of lenses are not enough permeable tothe oxygen. As a result, the cornea is unable to "breathe" properly.Consequently, after a period of time, the cornea becomes irritated orperhaps even damaged. Moreover, the lenses sometime tend to adhere tothe eye of the wearer after being in place for an unduly long period oftime, and this can cause discomfort and even damage to the eye.

In view of the foregoing advantages of contact lenses, it would be evenfurther advantageous if there were a contact lens that possessed theknown advantages of machinability, dimensional stability, toughness andoptical clarity, and which were also sufficiently oxygen permeable to beworn by a user for an extended period, such as for several days, weeks,or even months or more. Users of such lenses could wear them forextended periods and still feel comfortable; could have good vision andnot risk injuring their eyes. Contact lenses which could be worn for anextended period would eliminate common problems with existing lenses.

The anticipated life of an extended duration contact lens would belengthened considerably. This is because the requirement for handlingwould be very greatly reduced. More sturdy lenses, such as known typesof hard lenses, are not susceptible to tearing or cracking, but can bescratched by frequent removal and insertion and cleaning, particularlyif they are dropped occasionally. Losing the lenses is a realisticpossibility which could be minimized substantially by having lenseswhich are removed weekly, or monthly, or at greater intervals.

Referring now to prior attempts to provide polymers with increasedoxygen permeability; normally, most or all such known polymers haveeither been too dimensionally unstable for satisfactory use, or have hadother disadvantages. For example, it is known to add significant amountsof additives normally intended to increase wettability. While suchmaterials are helpful in proper amounts, using excess amounts thereofhas often tended to cause proteinaceous matter to deposit on and impairthe transparency of the inner surface of the lens.

While numerous attempts have been made to improve the oxygenpermeability of both hard and soft contact lenses, the attempts have metwith only limited success, particularly in thicker lens. Moreover, manysoft lens material provides an environment which is highly suitable forbacterial growth, and this calls for sterilization procedures which inturn require the lenses to be handled frequently.

The present invention, therefore, is intended from the standpoint of anend use product to provide contact lens materials which are sufficientlyoxygen permeable that they may be worn by the user on a greatly extendedbasis in relation to prior art lenses, which do not have thedisadvantages associated with known prior art lenses intended for thispurpose.

Referring now to its chemical aspects, the invention relates to themanufacture of copolymers of an acrylic or methacrylic material of aknown type and novel, silicone substitute acrylic or methacryliccompounds so as to produce an oxygen permeable plastic material which isuniquely suitable for manufacturing novel corneal contact lenses asreferred to above. The expression "copolymers" is sometimes used hereinfor simplicity in referring to a polymer which includes two principalcomonomers, although such polymer may incidentally include one or moreadditional known monomers in minor amounts for purposes such ascross-linking, increasing the wettability of the final product, orotherwise.

The copolymer compositions and products made therefrom are improved overcounterpart prior art compositions by reason of increased dimensionalstability and improved gas permeability. Such novel compositions alsoretain or provide improvements in desirable prior art characteristicssuch as optical clarity, the ability to be cast, molded and machined,and compatability with chemically bonded, hydrophilic materials adaptedto improve the wettability of the finished product.

Preferably, the compositions comprise high molecular weightpolysiloxanylalkylesters of acrylic and methacrylic acids and othercompositions as monomers, copolymerized with methacrylates or otheresters of acrylic or methacrylic acids, vinyl carbazole, vinyl benzenes,vinyl pyrrolidinone and itaconate esters.

According to the invention, one comonomer (the "first" comonomer) is anacrylic or methacrylic ester silane, substituted with one or more highlysubstituted siloxanyl group. One such typical comonomer isbis(trimethylsiloxy)methylsiloxanylbis(trimethylsiloxy)methacryloxypropylsilanewhich can be copolymerized with an alkyl acrylate or alkyl methacrylate,(the "second" comonomer), with this copolymer composition in turn beingcross-linked to a slight degree by cross-linking agents, and preferablyfurther modified by the addition of compounds intended to increase thewettability of the finished copolymer material. This basicpolymerization of the novel comonomers with known comonomers occursthrough a known double-bond polymerization mechanism.

A certain proportion, such as 10% to 60% of this compound is thenpolymerized with one or more or other second comonomer compounds havingthe same or similar acrylic or methacrylic ester portion, together withthe minor amounts of cross-linking and wetting agents, referred toabove.

One more aspect of the present invention relates to the method of makingthe so-called first or novel comonomers of the invention. According tothis method, chlorosilanes are reacted with hydroxy derivatives ofpolysiloxanyl groups, in the presence of pyridine to bond releasedhydrochloric acid in the form of precipitated salt of pyridiniumhydrochloride at low temperatures. The details of this method arebrought out in other portions of the specification. In still anotheraspect, the invention relates to alternate methods of preparing theabove or similar products. One alternate method comprises reactingothers, mono-, di-, or methacryloxypropyltrichlorosilanes with an excessof pyridine and reacting the resulting intermediates with polysilanolspentamethyldisiloxanol, heptamethylisotrisiloxanol(3-hydroxyheptamethyltrisiloxane) and trimethylsilanol at about -50° C.

A monomer is removed from these reaction mixtures by purificationfollowing removal of the low molecular weight materials with thereaction products being purified by washing with weak alkalies or likematerials.

The novel comonomer compounds of the present invention can berepresented by the following formulas: ##STR1## where n is an integer 1,2 or 3. and by: ##STR2## where n is an integer 1, 2 or 3. and by:##STR3## where n is an integer 1, 2 or 3.

In the alkyl or phenyl ester second principal comonomer, the alkyl groupcontains 1 to about 10 carbon atoms, (typically 1 to 6 carbon atoms) andthe phenyl ester contains a singly vinyl benzene, divinyl benzenes, anditaconate esters.

One compound which may be used as the first principal comonomer of thepresent invention is bis(trimethylsiloxy)methylsiloxanylbis(trimethylsiloxy)methacryloxypropylsilane: ##STR4## another compoundisbis{bis(trimethylsiloxy)methylsiloxanyl}-trimethylsiloxymethacryloxypropylsilane:##STR5## One more suitable compound isbis(trimethylsiloxy)methylsiloxanylmonopentamethyldisiloxanylmonotrimethylsiloxanylmethacryloxypropylsilane:##STR6##

Representative known or second comonomers which may be employed in thepractice of the invention include the following:

methyl acrylate, methyl methacrylate

ethyl acrylate, ethyl methacrylate

propyl acrylate, propyl methacrylate

isopropyl acrylate, isopropyl methacrylate

2-ethylhexyl acrylate, 2-ethylhexyl methacrylate

cyclohexyl acrylate, cyclohexyl methacrylate

benzyl acrylate, benzyl methacrylate

phenyl acrylate, phenyl methacrylate

n-vinyl carbazole, n-vinyl pyrrolidinone

3-hydroxy 2-naphtyl methacrylate

ethyl vinyl benzene, divinyl benzenes

dimethyl itaconate, diphenyl itaconate

and dihexylitaconate.

Cross-linking monomers include difunctional compounds such as:

ethyleneglycoldimethacrylate

diethyleneglycoldimethacrylate

triethyleneglycoldimethacrylate

tetraethyleneglycoldimethacrylate

polyethyleneglycoldimethacrylate

divinyl benezene

tetramethyldisiloxanyldi(methylmethacrylate)

and mixtures thereof.

The wetting agents include, but are not limited to:

acrylic acid

methacrylic acid

n-vinyl 2-pyrrolidine, and

hydroxyalkyl esters of acrylic and methacrylic acids,

and mixtures thereof.

In view of the shortcomings of prior art contact lenses and thecompounds and compositions used in making them, it is an object of thepresent invention to provide novel monomers useful in making improvedlens materials, improved polymer compositions made from such novelmonomers, and improved lenses made from such polymers.

Another object of the invention is to provide novel silicone compoundsused as components of polymerizable monomers.

And still another object is to provide highly branched or substitutedsiloxane materials for a variety of uses, including the manufacture ofcopolymers, terpolymers or other polymer incorporating such materials.

A still further object is to provide one or more compounds containingalkyl esters of acrylic or methacrylic acids, and incorporating threepolysiloxanylalkyl groups.

Another object is to provide an optically useful, novel polymericmaterial of increased oxygen permeability with respect to prior artcompounds.

And another object is to provide a composition which will make possiblethe manufacture of corneal contact lenses which can be worn for anextended time period while providing greatly increased comfort to thewearer.

Another object is to provide a polymeric contact lens material which iscompatible with additives of known kinds used to provide other desirableend use properties.

A still further object is to provide a method of manufacturingcopolymers incorporating the compositions made by the novel methodsreferred to above.

These and other objects and advantages of the invention, including thoseinherent therein, may be achieved in practice by carrying out themethods, and making the compounds and compositions referred to herein.The following examples, which are set forth by way of illustration andnot by way of limitation, illustrate preferred methods of carrying theinvention into practice.

DESCRIPTION OF THE PREFERRED EMBODIMENTS OF THE INVENTION EXAMPLE 1

This example illustrates a preparation of a new and useful monomer,bis(trimethylsiloxanyl)bis(trimethylsiloxy)methylsiloxanylmethacryloxypropylsilane.

Trichloromethacryloxypropylsilane (one mole) is dissolved in 700 ml ofdry diethylether and placed in a 5 liter, 3 necked, round bottom flaskequipped with a mechanical stirrer, a thermometer and an additionalfunnel. The solution is cooled down to -50° C. with a dryice-isopropanol cooling bath. When the temperature has reached -50° C.,280 grams (slight excess) of dry pyridine is added over a period ofabout 2 hours, with the temperature being held at -50° C. or less duringpyridine addition. At the same temperature, two moles oftrimethylsilanol and one mole of heptamethylisotrisiloxanol(3-hydroxyheptamethyltrisiloxane), which are prepared by known methodsin the art, is added in a diethylether solvent, forming a whiteprecipitate of pyridinium hydrochloride. When all the mixtures of thesilanols have been added, the temperature of the reaction mixture isincreased rapidly to about +30° C. and stirred for 1/2 hour. Thepyridinium hydrochloride is isolated by filtration and the filter cakeis washed with diethylether.

The crude monomer bis(trimethylsiloxanyl)bis(trimethylsiloxy)methylsiloxanylmethacryloxypropylsilane indiethylether is washed twice with water (200 ml each). The upper(organic) layer is then separated and diethylether is removed by meansof distillation. The crude monomer (I) is washed with 150 ml ofdistilled water, and thereafter twice with a dilute sodium bicarbonatesolution, again with distilled water once, and then dried over anhydrousmagnesium sulfate for 2 hours. The dried monomer is purified bydistilling off all low boiling materials at 85° C. and 0.1 mm Hgpressure. The purified monomer is refrigerated until used. Density ofthe monomer (I) is 0.98 g/ml at 20° C. and n² _(D) ⁵ =1.4153±0.0010.

EXAMPLE 2

This example illustrates a preparation of a new and useful monomer,bis{bis(trimethylsiloxy)methylsiloxanyl}monotrimethylsiloxanylmethacryloxypropylsilane.

One mole of trimethoxymethacryloxypropylsilane (248.0 g.), one mole ofacetoxytrimethylsilane and two moles of 3-acetoxyheptamethyltrisiloxaneare mixed together in a 2 liter, 3 necked, round bottom flask equippedwith a mechanical stirrer, a thermometer, and an additional funnel. Themixture is cooled to less than 10° C. by an ice cooling bath.

57.0 grams of aqueous ethanoic sulfuric acid are added to the reactionmixture over a period of 70 minutes. Then the temperature is slowlyincreased to room temperature, and the reaction mixture is stirred for16 hours. The aqueous layer which separates is removed and discarded.The organic layer is washed twice with 300 ml. of distilled water, andthereafter twice with a dilute sodium bicarbonate solution, again withdistilled water once, and then dried over magnesium sulfate (anhydrous)for 2 hours. The dried monomer is purified by distilling off all lowboiling materials at 80° C. and 0.1 mm Hg pressure. The purified monomeris refrigerated until used. Density of the monomer (II) is 0.965 g/ml at25° C.

EXAMPLE 3

This example illustrates the preparation of a representative oxygenpermeable copolymer.

A mixture of 38 parts of the comonomer (I) of Example 1, 57 parts ofmethyl methacrylate, 3 parts of methacrylic acid and 2 parts oftriethyleneglycoldimethacrylate and 0.14% by weight of the entiremixture of t-butyl peroxypivalate is placed in a glass dish or tube andthen placed in a vacuum oven which has been purged with nitrogen. Theoven is closed and the temperature is maintained at 48° C. for 24 hours.The monomers react to create a copolymer plastic which is hard,colorless, transparent and rigid. The oxygen permeability is 18.0×10⁻¹¹(cm² /sec) (ml O₂ /ml×mm Hg). The oxygen permeability of a disc ofpolymethylmethacrylate, measured in the same way is less 0.2×10⁻¹¹ (sameunits).

EXAMPLE 4

This example illustrates the preparation of a representative oxygenpermeable copolymer from another comonomer (III).

A mixture of 35 parts of novel comonomer (III), (which can be that,prepared by the chemistry described in Example 1 or 2), 50 parts ofmethyl methacrylate, 10 parts of cyclohexyl methacrylate, 2 parts ofn-vinyl pyrrolidone and 3 parts of triethyleneglycoldimethacrylate and0.25% by weight of the entire composition of t-butyl peroxydecanoate ispolymerized in a polypropylene dish or tube at 50° C. for 24 hours. Theresulting copolymer plastic material is machined, cut, polished, andfinished into a concavoconvex lens of 0.10 mm thickness. The oxygenpermeability of this lens is 26.6×10⁻¹¹ (cm² /sec)(ml O₂ /ml×mm Hg).

The following Examples 5-10 illustrate the conditions of preparation andproperties of copolymers which contain varying proportions of the novelcomonomer (II) of Example 2 when such comonomers are reacted with one ormore of the following compounds:

methyl methacrylate (MMA)

cyclohexyl methacrylate (CHMA)

methacrylic acid (MAA)

n-vinyl pyrrolidone (NVP)

triethyleneglycoldimethacrylate (Tri-EGDMA)

tetraethyleneglycoldimethacrylate (TEGDMA)

ethyleneglycoldimethacrylate (EGDMA)

The siloxane comonomer used in these examples is that prepared inExample 2, namely,bis{bis(trimethylsiloxy)methylsiloxanyl}mono(trimethylsiloxanyl)methacryloxypropylsilaneand which is abbreviated in the table below as C(II).

The polymerization is conducted in polypropylene tubes for 24 hours atthe temperature shown in the table. The table also shows the compositionof each form of polymer, and the temperature at which polymerizationtook place. The properties of the polymer are abbreviated in the righthand corner, with the meanings of the abbreviations appearing below.

In the examples, the principal polymers are C(II) and MMA, with thecompositions including one or more other compounds as indicated. MAAprovides wettability, CHMA supplements the MMA to accomplish betterrigidity, and NVP provides increased wettability, except that, wheremore than 4 or 5% NVP is present, a portion thereof serves as a thirdmonomer. The TEGDMA, Tri-EGDMA, and EGDMA are cross-linking agents.

    __________________________________________________________________________    COMPOSITION, WT., PERCENT                                                                              Tri-              TEMP                               Example                                                                            C(II)                                                                             MMA CHMA MAA NVP                                                                              EGDMA TEGDMA                                                                              EGDMA °C.                                                                        PROP.                          __________________________________________________________________________    5    42  27  27   2                  2     43  T,H,R                          6    60      40                            45  T,H,R                          7    40  50  10                            50  T,H,R                          8    35  57   3   3                  2     49  T,H,R                          9    45  35  10   4   2  4                 45  T,H,R                          10   38  45  10   3            4           47  T,H,R                          __________________________________________________________________________     T = Transparent                                                               H = Hard                                                                      R = Rigid                                                                

Products of the invention herein described as "hard" have a hardness,measured on the Shore D scale of about 84-90, (ASTM 2240) whilepolymethylmethacrylate, tested the same way, has a hardness of 90-93.

EXAMPLE 11

This example illustrates the preparation and properties of a wettable,oxygen permeable polymer. A disc is prepared in the manner described inExample 4 from a mixture of 40 parts of the monomer (I), Example 1, 40parts of methyl methacrylate, 4 parts of methacrylic acid and 16 partsof dimethyl itaconate, using t-butylperoxypivalate as a catalyst. Thepolymerization is carried out at 48° C. for 24 hours. The resulting discis colorless, transparent, hard and rigid. The oxygen permeability (Dkvalue) of the polymer is 15.3×10⁻¹¹ (cm² /sec)(ml O₂ /ml mm Hg). In thisexample, no difunctional cross-linking agent was used.

EXAMPLE 12

This example illustrates the preparation of a copolymer of methylmethacrylate and the mixture of novel comonomers, (I and II), 50/50,referred to in Example 1 and 2.

A cylindrical plug of the copolymer is prepared by polymerizing amixture of 40 parts of such novel comonomers, 50 parts of methylmethacrylate, 4 parts of NVP and 6 parts of divinyl benzene, in thepresence of t-butylperoxydecanoate at 45° C. The polymer plastic ishard, rigid, and highly oxygen permeable in relation to prior artmaterial.

The previous examples illustrate the outstanding properties of theresulting polymers of this invention. In great measure these propertiesare attributed to the novel comonomers.

Other additives to the polymers of this invention as known in the artcan be made. In all cases, the polymers are optically clear andtransparent and meet required standards of desirable high oxygenpermeability in semi-rigid and rigid contact lenses.

Even though I have described specific examples of this invention, thereare many variations possible within the scope of keeping the physicalproperties as previously described. Such variations include the use ofmixtures of monomers within the components to comprise of the requiredparts of each. For example, two or more siloxanyl alkyl ester comonomerscan be used instead of a single such comonomer for the component of thecomposition. Respectively, two or more cross-linking agents can be used.Other additives to the copolymers such as colorants, tints and likematerials may also be employed within the scope of normal ranges of thisinvention.

What is claimed is:
 1. An oxygen permeable hard or semi-hard,machinable, dimensionally stable, wettable contact lens material of hightransparency consisting essentially of polymer formed by free radicalpolymerization of(a) 15 to 60% by weight of at least one monomerselected from the group consisting ofbis(trimethylsiloxy)methylsiloxanylbis(trimethylsiloxy)methacryloxypropylsilane having the followingformula ##STR7##bis[bis(trimethylsiloxy)methylsiloxanyl]trimethylsiloxymethacryloxypropylsilanehaving the following formula ##STR8## andbis(trimethylsiloxy)methylsiloxanylmonopentamethyldisiloxanylmonotrimethylsiloxanylmethacryloxypropylsilanehaving the following formula ##STR9## (b) 40 to 85% by weight of atleast one acrylic or methacrylic acid ester comonomer selected from thegroup consisting of methyl acrylate, methyl methacrylate, ethylacrylate, ethyl methacrylate, propyl acrylate, propyl methacrylate,isopropyl acrylate, isopropyl methacrylate, 2-ethylhexyl acrylate,2-ethylhexyl methacrylate, cyclohexyl acrylate, cyclohexyl methacrylate,benzyl acrylate, benzyl methacrylate, phenyl acrylate, phenylmethacrylate, 3-hydroxy 2-naphtyl methacrylate, and mixtures thereof,(c) 10 to 30% by weight of at least one itaconic acid ester comonomerselected from the group consisting of dimethyl itaconate, diphenylitaconate and dihexyl itaconate, (d) 1 to 20% by weight of at least onehydrophilic comonomer selected from the group consisting of n-vinyl2-pyrrolidine, methacrylic acid and acrylic acid, and (e) 1 to 10% byweight of at least one cross-linking comonomer selected from the groupconsisting of ethyleneglycoldimethacrylate,diethyleneglycoldimethacrylate, triethyleneglycoldimethacrylate,tetraethyleneglycoldimethacrylate, polyethyleneglycoldimethacrylate,divinyl benzene, and tetramethyldisiloxanyldi(methylmethacrylate), said% by weight of (a), (b), (c), (d) and (e) being % by weight based on thetotal weight of (a), (b), (c), (d) and (e).
 2. An oxygen permeable hardor semi-hard, machinable, dimensionally stable, wettable contact lensmaterial of high transparency consisting essentially of copolymer formedby free radical polymerization of(a) 15 to 60% by weight of at least onemonomer selected from the group consisting ofbis(trimethylsiloxy)methylsiloxanylbis(trimethylsiloxy)methacryloxypropylsilane,bis[bis(trimethylsiloxy)methylsiloxanyl]trimethylsiloxymethacryloxypropylsilaneandbis(trimethylsiloxy)methylsiloxanylmonopentamethyldisiloxanylmonotrimethylsiloxanylmethacryloxypropylsilane,(b) 40 to 85% by weight of at least one acrylic or methacrylic acidester comonomer selected from the group consisting of methyl acrylate,methyl methacrylate, ethyl acrylate, ethyl methacrylate, propylacrylate, propyl methacrylate, isopropyl acrylate, isopropylmethacrylate, 2-ethylhexyl acrylate, 2-ethylhexyl methacrylate,cyclohexyl acrylate, cyclohexyl methacrylate, benzyl acrylate, benzylmethacrylate, phenyl acrylate, phenyl methacrylate, 3-hydroxy 2-naphtylmethacrylate, and mixtures thereof, (c) 1 to 20% by weight of at leastone hydrophilic comonomer selected from the group consisting of n-vinyl2-pyrrolidine, methacrylic acid and acrylic acid, and (d) 1 to 10% byweight of at least one cross-linking comonomer selected from the groupconsisting of ethyleneglycoldimethacrylate,diethyleneglycoldimethacrylate, triethyleneglycoldimethacrylate,tetraethyleneglycoldimethacrylate, polyethyleneglycoldimethacrylate,divinyl benzene, and tetramethyldisiloxanyldi(methylmethacrylate), said% by weight of (a), (b), (c) and (d) being % by weight based on thetotal weight of (a), (b), (c) and (d).